The principal goal of this project is to elucidate the structure and biological significance of an insulin-like protein in human serum. This protein has been purified from bank blood plasma and chemically characterized. It is presently termed the nonsuppressible insulin-like protein (NSILP) to distinguish it from insulin and smaller molecular weight peptides possessing growth promoting activity. NSILP is a 90,000 mol. wt. glycoprotein with a sedimentation coefficient of 4.72S. It is remarkably similar to transferrin and haptoglobin 1-1, but amino acid analysis clearly distinguishes it by its high arginine and tryptophan content. An immunoassay for NSILP has been developed that reveals a normal human serum concentration of 2-4 micrograms/ml. Additional antiserum studies verified that NSILP comprised 85-95% of the total serum NSILA. Fat cell receptor studies demonstrated that NSILP and insulin did not compete for the same receptor; instead, a positive cooperative effect was discovered. At the present time the main research effort is directed at characterizing the significance of the physiological interaction between insulin and NSILP.